6b1i | pdb_00006b1i

Disrupted hydrogen bond network impairs ATPase activity in an Hsc70 cysteine mutant

spinqualitylabelsall models 6b1i, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6b1i is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: ADP, GOL, MG, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HSP7C_HUMAN Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Publication Abstract from PubMed The ATPase domain of the 70-kD heat shock protein (Hsp70) family members shows a high degree of sequence, structural, and functional homology across species. A broadly conserved residue within the Hsp70 ATPase domain that captured our attention is an unpaired cysteine, positioned proximal to the site of nucleotide binding. Prior studies of several Hsp70 family members show this cysteine is not required for Hsp70 ATPase activity, yet select amino acid replacements of the cysteine can dramatically alter ATP hydrolysis. Moreover, post-translational modification of the cysteine has been reported to limit ATP hydrolysis for several Hsp70s. To better understand the underlying mechanism for how perturbation of this non-catalytic residue modulates Hsp70 function, we solved the structure for a cysteine-to-tryptophan mutation in the constitutively-expressed mammalian Hsp70 family member Hsc70. Our work reveals that the steric hindrance produced by a cysteine-to-tryptophan mutation disrupts the hydrogen-bond network within the active site resulting in a loss of proper catalytic magnesium coordination. We propose that a similarly altered active site is likely observed upon post-translational oxidation. We speculate that the subtle changes we detect in the hydrogen-bonding network may relate to the previously reported observation that cysteine oxidation can influence Hsp70 inter-domain communication. Disrupted hydrogen bond network and impaired ATPase activity in an Hsc70 cysteine mutant.,O'Donnell JP, Marsh HM, Sondermann H, Sevier C Biochemistry. 2018 Jan 4. doi: 10.1021/acs.biochem.7b01005. PMID:29300467 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Protein structures

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